CREM遺伝子:代替のDNA結合ドメインを使用すると,cAMP誘発の転写の複数のアンタゴニストが生成されます
N S Foulkes1, E Borrelli, P Sassone-Corsi
1Laboratoire de Génétique Moléculaire des Eucaryotes du CNRS, Faculté de Médecine, Strasbourg, France.
Cell
|February 22, 1991
まとめ
研究者らは,マウスの下垂体細胞にあるCREMという遺伝子を発見し,アクティベーターCREBと異なり,cAMP誘発の転写を抑制する作用をしている. この新しい遺伝子は,細胞特異的な発現と代替スプライシングを示し,遺伝子調節に関する新しい洞察を提供します.
科学分野:
- 分子生物学は分子生物学である.
- 遺伝子規制 遺伝子規制
- セルラー・シグナリング
背景:
- 循環型AMP反応性要素結合タンパク質 (CREB) は,cAMP反応性プロモーター要素 (CREs) の活性化剤として知られています.
- CREBの発現は,さまざまな細胞タイプにおいて一般的に均一である.
- 細胞特異的な方法でcAMP誘発転写を調節する正確なメカニズムについては,さらなる解明が必要である.
研究 の 目的:
- cAMP媒介による遺伝子調節に関与する新しい遺伝子を特定し,特徴づけること.
- CREBのホモログの表現パターンと機能的役割を調査する.
- 細胞特異の転写制御の分子基礎を理解するために.
主な方法:
- マウスの下垂体cDNAライブラリを分離した.
- ポリメラーゼ連鎖反応 (PCR) とmRNA同型識別のためのRNA酶保護分析.
- 特定されたmRNAアイソフォームのDNAシーケンシング.
- CRE配列に対するDNA結合効率と特異性の評価.
主要な成果:
- CREM (cAMP反応性要素調節器) と呼ばれる新しい遺伝子が分離され,CREB.に同類するタンパク質をコードする.
- CREMは細胞特異的な発現を示し,CREBの均一な発現とは対照的です.
- CREMは,下流,枠外DNA結合ドメインを持つユニークな構造組織を有しています.
- 異なる細胞特異のスプライシングは,DNA結合ドメインの代替使用で少なくとも3つのmRNAアイソフォームを生成します.
- CREMは,CREBと同様の効率と特異性を持つCRE配列と結合する.
- CREBとは異なり,CREMはcAMP誘発による転写のダウンレギュレータとして機能します.
結論:
- CREMは,cAMP誘発トランスクリプションの新しい細胞特異的調節剤です.
- CREMトランスクリプトの代替スプライシングは,遺伝子調節における機能的多様性につながる.
- CREMは,トランスクリプション抑制剤として作用し,CREBの活性化作用をバランスとします.
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